1. Field of the Invention
The present invention relates to a method for storing and retrieving temporal information and applications thereof including devices that use the method of distributing temporal information into arrays of spatial patterns and a method of detecting the efficacy of drugs, toxic substances or treatments on human memory and other cognitive processes.
2. Brief Description of the Related Art
Brief Description of Prior Model: The new design derives loosely from a model the present inventor published of memory functions in the brain (Landfield, 1976). However, the prior model did not address storage of sequential information sets and the emergent elements of the updated model that deal with distribution and storage of temporal information represent a new invention that is not inherent in the prior model. The original model (Landfield, 1976) proposed that memory traces are formed in a neuron in which excitation generated by a non-information containing synchronous EEG wave occurs at approximately the same time as excitation from information-containing impulses arriving over other inputs. The summation of excitation from the two inputs is sufficient to activate the receiving neuron to fire impulses, which then leave lasting traces (memory) in that neuron as well as activate the next neurons in the chain. Because the model relies on summation between two brain waves, this process was noted to be somewhat analogous to the interference patterns formed by two coherent light beams (e.g., laser beams) projected onto a screen, which form light stripes where the wave maxima are in phase, and dark stripes where the wave maxima are out of phase and cancel. These optical patterns are often termed xe2x80x9cinterference fringes.xe2x80x9d In addition, because the formation of holograms depends on such interference patterns between a coherent xe2x80x9creference beamxe2x80x9d (usually a monochromatic laser beam) and a coherent xe2x80x9cobject beamxe2x80x9d part of the laser beam that is split and reflected off of the object of which the holographic representation is being made), the brain model was also noted to be partly analogous to the interference pattern-holographic process of optics (Landfield, 1976).
However, the nature of neural information is of course substantially different from the phase information carried in reflected light beams in holograms, and some important conceptual differences exist between the brain model and holography. One difference is that, in the brain model, each EEG wave functions as a sampling and encoding mechanism that samples the amount of activity in a neuron within some time frame (generally, the excitatory phase of the EEG wave); that is, the information activity being processed in an assembly of neurons summates with the EEG wave, which is modified in each neuron proportionally to the degree of informational activity stimulating that neuron. The modified wave then transports that encoded xe2x80x9ctime-slicexe2x80x9d of information as it travels through the brain. The next wave of the EEG rhythm captures the next xe2x80x9cslicexe2x80x9d of temporal information.
Many brain models for processing temporal information have been proposed, but very few deal with long term memory storage of that information. Those that do often propose the storage of sequential information in different oscillatory patterns or regions of the same neurons, or in different activity patterns in linked cell assemblies. However, it is highly difficult or not feasible to store temporally-tagged information in the same neurons.
Utility of the Invention At present, there are massive efforts underway at many pharmaceutical firms to develop new drugs for the improvement of memory, aimed at elderly or neurologically impaired individuals, and perhaps eventually at healthy young adults as well. One of the major problems of this drug development work, however, is that there are no rapid screening methods for testing efficacy of drugs on memory. The animal models used can be controversial and the data are not always generalizable to humans; in addition, the present cellular models being developed (e.g., long-term potentiation) are even more controversial (see Russo, xe2x80x9cThe Scientistxe2x80x9d Vol 13, March, 1999).
If the model proposed here is even partially accurate, then it could be used to test the phase shifting, intensity of summation, and rates of travel of excitation through the hippocampus, either in in vitro organotypic brain slices or in animals chronically implanted with standard electrode arrays or other preparations, and therefore could potentially function as an extremely sensitive and accurate screening procedure for development of drugs that influence memory and perhaps other cognitive processes. Moreover, the method could be used by defense, medical, or environmental agencies of companies to detect or evaluate neurotoxic agents that impair memory.
Most electronic memory systems (computers) involve random access memories, in which information sets are stored in available sites and lose sequential information (other than date codes that must be interpreted by the user). The construction of devices that could learn, store and retrieve sequential information in a temporally ordered fashion, therefore, might have vast utility at which we can only begin to guess. This temporal learning capacity might, for example, vastly improve computer graphics or reprogramming of devices based on experience of operation; architectural or industrial designs will also benefit; instrument glitches or errors will be more readily self-corrected; numerous entertainment uses (computer games, holographic graphics, etc.) are also envisioned.
There have been and are intensive major efforts by defense and various research and industrial establishments to develop devices that can learn based on neural network principles. Clearly, the incorporation of a process for learning and storing temporally ordered information would be a major advantage for these efforts. The full range of possible applications is difficult to envision but it can be expected to be extensive based on the recent explosive developments in the electronic/optical industries.
The new aspect of the model deals with how the brain distributes the traveling informational xe2x80x9ctime slicesxe2x80x9d (waves) for storage in different, spatially-distinct neuronal arrays. The present invention stems from the realization that while it is highly difficult or not feasible to store temporally-tagged information in the same neurons, different time-linked information sets are more efficiently stored in separate spatially-distinct arrays of neurons. To accomplish this, we suggest that the brain sends the information-containing wavefronts along sheets of parallel fibers, each of which fiber synapses on (connects to) many dozens to hundreds of neurons sequentially (through synapses of passage).
As new information continuously passes along these parallel fibers, it is not intense enough by itself to activate the neurons to which the axon fibers connect sequentially unless these neurons are also activated simultaneously by another beam of excitation from a separate input source; that is, unless summation occurs. In the model, this separate xe2x80x9cbeam of excitationxe2x80x9d comes from the excitatory phase of a synchronized EEG wave. As the EEG wave sweeps over an array of neurons, all neurons in that array are near-simultaneously depolarized (excited) by synchronized synaptic inputs. This excitation brings them close to threshold for firing impulses. Then, if intense impulses encoding information (high frequencies of firing) arrive over the parallel fiber lines in the same time window of peak EEG excitation, they will summate with the EEG excitation and fire the neurons. Because the excitation generated by the EEG wave is generally equivalent in each neuron, the activation of target neurons will occur proportionally to the intensity of activity on each parallel fiber.
The new principle for temporal storage is that the distribution in separate neuron arrays of temporally sequential information sets is accomplished by the timed, incremental shifting of the xe2x80x9creference beam of synchronized excitationxe2x80x9d (excitatory phase of the EEG wave) along the long axis of the parallel fibers, in the plane of information travel. This shift allows the next array of neurons to be brought close to threshold just as the next set of temporal information arrives, thereby enabling it to respond to (through summation) the information input. A further shift of the xe2x80x9creference beam of excitationxe2x80x9d along the axis of wave travel can xe2x80x9cprimexe2x80x9d or xe2x80x9cenablexe2x80x9d still another array along the parallel fibers, such that the next information set activates only that next array of neurons, and so on.
The timed, incremental shift of the xe2x80x9creference beam of excitationxe2x80x9d along the axis of information travel (parallel fibers) can theoretically occur at any rate which is compatible with the rates of information transmission and storage appropriate for that system. In the brain model, however, the shift is synchronized in time such that the next sequential array is xe2x80x9cenabledxe2x80x9d (excited) by the reference beam just as the next information-containing rhythmic EEG wave (xe2x80x9cinformation beamxe2x80x9d) arrives over the parallel fibers at the same array.
In the brain model, the phase shift in xe2x80x9creference excitationxe2x80x9d is accomplished by sequential delays in the activation of the intemeurons that generate the EEG wave. However, for purposes of the invention, any mechanism that incrementally shifted a xe2x80x9cprocess of enablementxe2x80x9d along the axis of informational content travel would be equivalent.
Similarly, whereas the mechanism of xe2x80x9cenablementxe2x80x9d of neural arrays in the brain model is summation of excitation in neurons, any other mechanism that selectively brought an array of storage elements to a responsive (enabled) state, and did so in spatially distinct arrays in a temporally incremental manner such that different arrays responded to different information sets sequentially, would be equivalent for purposes of the invention.
In the nervous system, equivalent enabling processes to the EEG rhythm mechanism proposed could, for example include rebounds from inhibition, biochemical changes at synapses, or recurrent collateral excitation, among others. In instrument devices built on these principles, equivalent processes could include electrical biases on element inputs, photonic activation, modulation of circuit switches, or mechanical switching, among many other possibilities.
These examples would be equivalent because the essential factor of the invention, whether biological or electronic, is a timed, incrementally shifting state of response enablement along the direction of information set travel, such that multiple spatially distinct arrays of response/storage elements become responsive in an orderly sequence. With this process, selected arrays become sequentially enabled in time and space to respond to or store temporally ongoing information sets that pass by the arrays over time. Thus, this mechanism allows the sequential xe2x80x9ccapturexe2x80x9d of different xe2x80x9ctime slicesxe2x80x9d of information from a continuous flow and distributes them in spatially distinct arrays of elements, with each spatial array becoming enabled and then unenabled in temporal sequence. In addition, any recall system that involved the sequential re-activation of these arrays, with the goal of retrieving the temporally ordered information, would be a subset of this invention.
Over 20 years ago, it was proposed that during the formation, storage and retrieval of memory traces, the hippocampal theta rhythm (HTR) functioned somewhat analogously to coherent laser beams in holography, that is by forming xe2x80x9cinterference patternsxe2x80x9d (Landfield, 1976 In: Molec. and Func. Neurobiol., Elsevier, W. H. Gispen, ed. P.390-424). This proposal was supported in part by evidence that electrically driving the HTR with xcx9c7Hz septal stimulation can facilitate memory consolidation (Landfield, Physiol. Behav. 1977; Destrade, Brain Res. 1982). Since then, there has been much evidence consistent with this model. The present invention is directed to the application of an update of the original model. Novel mechanisms for the sequential storage of temporally ordered information-containing wavefronts have been incorporated. As wavefronts are sequentially projected from dentate gyrus to CA1 at theta frequencies, it is proposed that spatially adjacent, longitudinally oriented arrays of pyramidal cells are sequentially enabled to respond to the waves, such that Wave 1 activates and is stored in Array 1, Wave 2 is then stored in the next array (Array 2), Wave 3 in Array 3, and so on. Thus temporal sequence is converted to spatial order. Sequential enablement is accomplished by a synchronized phase shift of the excitatory peak of theta along the transverse direction of wave travel which activates the next neuronal array as the next theta wave of information arrives. This shift is governed by a combination of inhibitory and excitatory interneurons that xe2x80x9cresetxe2x80x9d theta in the next array, and by afterhyperpolarizations that protect recently activated arrays from reactivation. This temporal memory process would function somewhat like a series of holographs that could be readily recreated in spatial sequence (retrieval).
In addition, memories in the brain undergo multiple steps of processing, including indexing, distillation, symbolic associations and incorporation into other sets of associations. These different levels or steps of processing can occur sequentially in different arrays of memory units. Therefore, another variation of this invention includes any system of spatially adjacent or spatially ordered arrays of memory elements that are enabled in sequence, in a manner synchronized with the transformation or the arrival of the next level of processing of an information series. This memory storage system therefore functions not only to store in adjacent arrays the different information traces of similar levels of organization that occur sequentially in time, but in addition, functions to store in adjacent arrays the different levels of organization and processing of the same information trace as these levels develop sequentially, not necessarily in temporal sequence.
For example, an information trace is stored in the first spatial array and, in addition to being stored, undergoes an important transformation, distillation, or other form of processing, and subsequently emerges in its new form from the initial array. This second processed form of the original information series is then stored in the second array of memory units (neurons or other elements). Furthermore, the second level of trace organization is subjected to additional processing and transformation, to a third level of organization, and so on. Each new level of organization is stored in a new spatial array of memory units which was either localized adjacently or otherwise ordered along connecting elements that ensured its orderly sequential enablement for storage and later, its orderly activation for recall of that new stage of information processing.
In one aspect, the invention comprises storage and recall systems that convert temporally sequential information into a predetermined spatial organization, based on xe2x80x9chard-wiredxe2x80x9d connections and/or programmed properties of the units and intra-array connections. This temporal information can involve sequential but different information patterns of the same level of organization (time slices) or it can involve sequential phases of processing/transformation and different levels of organization of the same original set of information.
One embodiment of the present invention relates to a method and memory device for storing temporally sequential information in an array of fixed interconnected memory storage units. Accordingly, the temporally sequential information is applied to the array of fixed interconnected memory storage units; and each of the fixed interconnected memory storage units is successively activated in sequence to store a corresponding time slice of the temporally sequential information.
An aspect of the method of the invention also includes recall of the different levels or phases of processing in an orderly sequential pattern of spatial activation (including forward or reverse activation), just as does recall of the temporal information (time slices) of similar levels of organization by orderly spatial activation.
Another aspect of the invention, the conversion of temporally sequential information patterns to a predetermined spatial organization of adjacent or otherwise spatially organized arrays of memory units that ensures the faithful sequential activation of the arrays, has been illustrated primarily with an example in which a beam of excitation or electrical bias, or other form of enablement, travels in the same direction of information or processing, sequentially enabling one spatially ordered array after another. However, neuronal arrays are usually interconnected with one another, and another form of the invention is if the activation of the first array of units was sufficient to activate the second (next) in sequence at the proper time to store the second information trace (time slice) or second level of processing, and then the activation of the second array units was sufficient to enable the 3rd array to store the 3rd (next) information set, and so on. In this variation, no extraneous incremental, synchronizing mechanism of enablement is necessary, because the sequential enablement would be governed by the pre-wired connections between the different arrays. In this variation, storage and/or processing of information in the first array would automatically enable the next (second) array in preparation for storing/processing the second (next) set or phase of information. The output connections of the first array would automatically ensure enablement of the second array in the appropriate time frame and pattern or would automatically transfer the processed set of information to the next spatial array in appropriate sequence.
Any pre-wired or pre-programmed intra-array connective system for enabling and/or activating adjacent, or functionally adjacent, spatial arrays of memory units in an orderly sequence for either storing or retrieving temporally sequential information sets such that meaningfill sequential information is retained is encompassed by this invention.
These and other objects of the invention will be more fully understood from the following description of the invention, the referenced drawings attached hereto and the claims appended hereto.